Quality of life for the more than 15 million people worldwide with drug-resistant epilepsy is tied to how precisely the brain areas responsible for generating their seizures can be localized. Current approaches to seizure localization are non-quantitative, and may include human interpretation of magnetic resonance and computed tomography images, neuropsychological test results, and scalp EEG recordings. In cases where these tests are suggestive of focal seizures but precise localization remains elusive, patients are often recommended for an invasive monitoring procedure, intracranial EEG (iEEG), in which recording electrodes are implanted within the skull cavity (typically beneath the dura mater) in order to improve signal fidelity.
Using the iEEG for seizure localization is subjective and labor-intensive. Neurologists trained to recognize stereotypical epileptiform and seizure patterns use commercial software to visualize multielectrode data streams that are often collected continuously over days or weeks. The goal is to manually identify putative channels (i.e., electrode recordings) showing earliest electrographic seizure onset. Qualitative information gleaned from iEEG screening is then used in planning the surgical procedure.
Surgeries based on these current approaches to localization are moderately effective. In one study, for example, focal tissue resections in medically refractory mesial temporal lobe epilepsy patients, guided by iEEG-determined clinical identification of the “seizure onset zone,” led to seizure freedom in about 50% of patients at 5 years post-operation. Furthermore, not all patients originally considered for surgery are ultimately deemed eligible: brain areas flagged for excision may overlap with regions vital to everyday functioning (e.g., speech, motor control, etc.), in which case they may not be safely removed.
The marginal outcomes of surgeries based on qualitative seizure localization and the preclusion of qualitative localization within real-time implantable systems (which promise to help patients who are ineligible for surgery) have prompted a search for quantitative signatures of epileptogenic brain. High Frequency Oscillations (HFOs), quasi-sinusoidal bursts of neurophysiological activity that persist for tens of milliseconds and have predominant energy in the frequency range between 100 and 500 Hz, have emerged as a leading candidate.
HFOs may be recorded using metal electrodes placed within the brain parenchyma; on the surface of the cortex, with or without one of the three meningeal layers—the dura mater, the arachnoid membrane, and the pia mater—interposing; or, less likely, on the surface of the skull bone; on the surface of the periosteum; or on the surface of the skin (i.e., the scalp). The recording electrodes typically are, but need not be, in direct physical contact with biological tissue, as the signals of interest may be transmitted capacitively.
The de facto standard in research settings for detection and classification of HFOs is human-intensive data marking. These manual approaches are both unreliable and infeasible within the time horizons for patient care in clinical settings. Described herein are systems, methods, and apparatus that address these problems.